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Mutagen-Specific Mutation Signature Determines Global microRNA Binding

Micro-RNAs (miRNAs) are small non-coding RNAs that regulate gene products at the post-transcriptional level. It is thought that loss of cell regulation by miRNAs supports cancer development. Based on whole genome sequencing of a melanoma tumor, we predict, using three different computational algorit...

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Autores principales: Greenberg, Eyal, Rechavi, Gideon, Amariglio, Ninette, Solomon, Oz, Schachter, Jacob, Markel, Gal, Eyal, Eran
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3212558/
https://www.ncbi.nlm.nih.gov/pubmed/22096567
http://dx.doi.org/10.1371/journal.pone.0027400
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author Greenberg, Eyal
Rechavi, Gideon
Amariglio, Ninette
Solomon, Oz
Schachter, Jacob
Markel, Gal
Eyal, Eran
author_facet Greenberg, Eyal
Rechavi, Gideon
Amariglio, Ninette
Solomon, Oz
Schachter, Jacob
Markel, Gal
Eyal, Eran
author_sort Greenberg, Eyal
collection PubMed
description Micro-RNAs (miRNAs) are small non-coding RNAs that regulate gene products at the post-transcriptional level. It is thought that loss of cell regulation by miRNAs supports cancer development. Based on whole genome sequencing of a melanoma tumor, we predict, using three different computational algorithms, that the melanoma somatic mutations globally reduce binding of miRNAs to the mutated 3′UTRs. This phenomenon reflects the nature of the characteristic UV-induced mutation, C-to-T. Furthermore, we show that seed regions are enriched with Guanine, thus rendering miRNAs prone to reduced binding to UV-mutated 3′UTRs. Accordingly, mutation patterns in non UV-induced malignancies e.g. lung cancer and leukemia do not yield similar predictions. It is suggested that UV-induced disruption of miRNA-mediated gene regulation plays a carcinogenic role. Remarkably, dark-skinned populations have significantly higher GC content in 3′UTR SNPs than light-skinned populations, which implies on evolutionary pressure to preserve regulation by trans-acting oligonucleotides under conditions with excess UV radiation.
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spelling pubmed-32125582011-11-17 Mutagen-Specific Mutation Signature Determines Global microRNA Binding Greenberg, Eyal Rechavi, Gideon Amariglio, Ninette Solomon, Oz Schachter, Jacob Markel, Gal Eyal, Eran PLoS One Research Article Micro-RNAs (miRNAs) are small non-coding RNAs that regulate gene products at the post-transcriptional level. It is thought that loss of cell regulation by miRNAs supports cancer development. Based on whole genome sequencing of a melanoma tumor, we predict, using three different computational algorithms, that the melanoma somatic mutations globally reduce binding of miRNAs to the mutated 3′UTRs. This phenomenon reflects the nature of the characteristic UV-induced mutation, C-to-T. Furthermore, we show that seed regions are enriched with Guanine, thus rendering miRNAs prone to reduced binding to UV-mutated 3′UTRs. Accordingly, mutation patterns in non UV-induced malignancies e.g. lung cancer and leukemia do not yield similar predictions. It is suggested that UV-induced disruption of miRNA-mediated gene regulation plays a carcinogenic role. Remarkably, dark-skinned populations have significantly higher GC content in 3′UTR SNPs than light-skinned populations, which implies on evolutionary pressure to preserve regulation by trans-acting oligonucleotides under conditions with excess UV radiation. Public Library of Science 2011-11-09 /pmc/articles/PMC3212558/ /pubmed/22096567 http://dx.doi.org/10.1371/journal.pone.0027400 Text en Greenberg et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Greenberg, Eyal
Rechavi, Gideon
Amariglio, Ninette
Solomon, Oz
Schachter, Jacob
Markel, Gal
Eyal, Eran
Mutagen-Specific Mutation Signature Determines Global microRNA Binding
title Mutagen-Specific Mutation Signature Determines Global microRNA Binding
title_full Mutagen-Specific Mutation Signature Determines Global microRNA Binding
title_fullStr Mutagen-Specific Mutation Signature Determines Global microRNA Binding
title_full_unstemmed Mutagen-Specific Mutation Signature Determines Global microRNA Binding
title_short Mutagen-Specific Mutation Signature Determines Global microRNA Binding
title_sort mutagen-specific mutation signature determines global microrna binding
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3212558/
https://www.ncbi.nlm.nih.gov/pubmed/22096567
http://dx.doi.org/10.1371/journal.pone.0027400
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